DRUG INTERACTIONS
Acetaminophen; Aspirin; Diphenhydramine: (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of other sedating medications, such as sedating H1-blockers.
Acetaminophen; Caffeine; Dihydrocodeine: (Contraindicated) Concomitant use of safinamide with opioids is contraindicated due to the risk of serotonin syndrome. Allow at least 14 days between discontinuation of safinamide and initiation of treatment with opioids.
Acetaminophen; Caffeine; Pyrilamine: (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of other sedating medications, such as sedating H1-blockers.
Acetaminophen; Chlorpheniramine: (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of other sedating medications, such as sedating H1-blockers.
Acetaminophen; Chlorpheniramine; Dextromethorphan: (Contraindicated) Dextromethorphan prescription products are contraindicated in patients taking monoamine oxidase inhibitors (MAOIs) or in patients who have taken MAOIs within the preceding 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. Allow at least 14 days after stopping dextromethorphan before starting an MAOI, including safinamide. Brief episodes of psychosis or bizarre behavior have also been reported with this combination. Patients should read nonprescription product labels carefully. Before initiating an MAOI after using other serotoninergic agents, a sufficient amount of time must be allowed for clearance of the serotoninergic agent and its active metabolites. (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of other sedating medications, such as sedating H1-blockers.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Contraindicated) Dextromethorphan prescription products are contraindicated in patients taking monoamine oxidase inhibitors (MAOIs) or in patients who have taken MAOIs within the preceding 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. Allow at least 14 days after stopping dextromethorphan before starting an MAOI, including safinamide. Brief episodes of psychosis or bizarre behavior have also been reported with this combination. Patients should read nonprescription product labels carefully. Before initiating an MAOI after using other serotoninergic agents, a sufficient amount of time must be allowed for clearance of the serotoninergic agent and its active metabolites. (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of other sedating medications, such as sedating H1-blockers. (Moderate) Severe hypertensive reactions, including hypertensive crisis, have been reported in patients taking monoamine oxidase inhibitors (MAOIs), such as safinamide, and sympathomimetic medications, such as phenylephrine. If concomitant use of safinamide and phenylephrine is necessary, monitor for hypertension and hypertensive crisis.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Contraindicated) Dextromethorphan prescription products are contraindicated in patients taking monoamine oxidase inhibitors (MAOIs) or in patients who have taken MAOIs within the preceding 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. Allow at least 14 days after stopping dextromethorphan before starting an MAOI, including safinamide. Brief episodes of psychosis or bizarre behavior have also been reported with this combination. Patients should read nonprescription product labels carefully. Before initiating an MAOI after using other serotoninergic agents, a sufficient amount of time must be allowed for clearance of the serotoninergic agent and its active metabolites. (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of other sedating medications, such as sedating H1-blockers. (Moderate) Severe hypertensive reactions, including hypertensive crisis, have been reported in patients taking monoamine oxidase inhibitors (MAOIs), such as safinamide concurrently with sympathomimetic medications, such as pseudoephedrine. If concomitant use of safinamide and pseudoephedrine is necessary, monitor for hypertension and hypertensive crisis.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of other sedating medications, such as sedating H1-blockers. (Moderate) Severe hypertensive reactions, including hypertensive crisis, have been reported in patients taking monoamine oxidase inhibitors (MAOIs), such as safinamide, and sympathomimetic medications, such as phenylephrine. If concomitant use of safinamide and phenylephrine is necessary, monitor for hypertension and hypertensive crisis.
Acetaminophen; Codeine: (Contraindicated) Concomitant use of safinamide with opioids is contraindicated due to the risk of serotonin syndrome. Allow at least 14 days between discontinuation of safinamide and initiation of treatment with opioids.
Acetaminophen; Dextromethorphan: (Contraindicated) Dextromethorphan prescription products are contraindicated in patients taking monoamine oxidase inhibitors (MAOIs) or in patients who have taken MAOIs within the preceding 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. Allow at least 14 days after stopping dextromethorphan before starting an MAOI, including safinamide. Brief episodes of psychosis or bizarre behavior have also been reported with this combination. Patients should read nonprescription product labels carefully. Before initiating an MAOI after using other serotoninergic agents, a sufficient amount of time must be allowed for clearance of the serotoninergic agent and its active metabolites.
Acetaminophen; Dextromethorphan; Doxylamine: (Contraindicated) Dextromethorphan prescription products are contraindicated in patients taking monoamine oxidase inhibitors (MAOIs) or in patients who have taken MAOIs within the preceding 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. Allow at least 14 days after stopping dextromethorphan before starting an MAOI, including safinamide. Brief episodes of psychosis or bizarre behavior have also been reported with this combination. Patients should read nonprescription product labels carefully. Before initiating an MAOI after using other serotoninergic agents, a sufficient amount of time must be allowed for clearance of the serotoninergic agent and its active metabolites. (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of other sedating medications, such as sedating H1-blockers.
Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Contraindicated) Dextromethorphan prescription products are contraindicated in patients taking monoamine oxidase inhibitors (MAOIs) or in patients who have taken MAOIs within the preceding 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. Allow at least 14 days after stopping dextromethorphan before starting an MAOI, including safinamide. Brief episodes of psychosis or bizarre behavior have also been reported with this combination. Patients should read nonprescription product labels carefully. Before initiating an MAOI after using other serotoninergic agents, a sufficient amount of time must be allowed for clearance of the serotoninergic agent and its active metabolites. (Moderate) Severe hypertensive reactions, including hypertensive crisis, have been reported in patients taking monoamine oxidase inhibitors (MAOIs), such as safinamide, and sympathomimetic medications, such as phenylephrine. If concomitant use of safinamide and phenylephrine is necessary, monitor for hypertension and hypertensive crisis.
Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Contraindicated) Dextromethorphan prescription products are contraindicated in patients taking monoamine oxidase inhibitors (MAOIs) or in patients who have taken MAOIs within the preceding 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. Allow at least 14 days after stopping dextromethorphan before starting an MAOI, including safinamide. Brief episodes of psychosis or bizarre behavior have also been reported with this combination. Patients should read nonprescription product labels carefully. Before initiating an MAOI after using other serotoninergic agents, a sufficient amount of time must be allowed for clearance of the serotoninergic agent and its active metabolites. (Moderate) Severe hypertensive reactions, including hypertensive crisis, have been reported in patients taking monoamine oxidase inhibitors (MAOIs), such as safinamide concurrently with sympathomimetic medications, such as pseudoephedrine. If concomitant use of safinamide and pseudoephedrine is necessary, monitor for hypertension and hypertensive crisis.
Acetaminophen; Dextromethorphan; Phenylephrine: (Contraindicated) Dextromethorphan prescription products are contraindicated in patients taking monoamine oxidase inhibitors (MAOIs) or in patients who have taken MAOIs within the preceding 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. Allow at least 14 days after stopping dextromethorphan before starting an MAOI, including safinamide. Brief episodes of psychosis or bizarre behavior have also been reported with this combination. Patients should read nonprescription product labels carefully. Before initiating an MAOI after using other serotoninergic agents, a sufficient amount of time must be allowed for clearance of the serotoninergic agent and its active metabolites. (Moderate) Severe hypertensive reactions, including hypertensive crisis, have been reported in patients taking monoamine oxidase inhibitors (MAOIs), such as safinamide, and sympathomimetic medications, such as phenylephrine. If concomitant use of safinamide and phenylephrine is necessary, monitor for hypertension and hypertensive crisis.
Acetaminophen; Dextromethorphan; Pseudoephedrine: (Contraindicated) Dextromethorphan prescription products are contraindicated in patients taking monoamine oxidase inhibitors (MAOIs) or in patients who have taken MAOIs within the preceding 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. Allow at least 14 days after stopping dextromethorphan before starting an MAOI, including safinamide. Brief episodes of psychosis or bizarre behavior have also been reported with this combination. Patients should read nonprescription product labels carefully. Before initiating an MAOI after using other serotoninergic agents, a sufficient amount of time must be allowed for clearance of the serotoninergic agent and its active metabolites. (Moderate) Severe hypertensive reactions, including hypertensive crisis, have been reported in patients taking monoamine oxidase inhibitors (MAOIs), such as safinamide concurrently with sympathomimetic medications, such as pseudoephedrine. If concomitant use of safinamide and pseudoephedrine is necessary, monitor for hypertension and hypertensive crisis.
Acetaminophen; Dichloralphenazone; Isometheptene: (Moderate) Severe hypertensive reactions, including hypertensive crisis, have been reported in patients taking monoamine oxidase inhibitors (MAOIs), such as safinamide, and sympathomimetic medications, such as isometheptene. If concomitant use of safinamide and isometheptene is necessary, monitor for hypertension and hypertensive crisis.
Acetaminophen; Diphenhydramine: (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of other sedating medications, such as sedating H1-blockers.
Acetaminophen; Guaifenesin; Phenylephrine: (Moderate) Severe hypertensive reactions, including hypertensive crisis, have been reported in patients taking monoamine oxidase inhibitors (MAOIs), such as safinamide, and sympathomimetic medications, such as phenylephrine. If concomitant use of safinamide and phenylephrine is necessary, monitor for hypertension and hypertensive crisis.
Acetaminophen; Hydrocodone: (Contraindicated) Concomitant use of safinamide with opioids is contraindicated due to the risk of serotonin syndrome. Allow at least 14 days between discontinuation of safinamide and initiation of treatment with opioids.
Acetaminophen; Oxycodone: (Contraindicated) Concomitant use of safinamide with opioids is contraindicated due to the risk of serotonin syndrome. Allow at least 14 days between discontinuation of safinamide and initiation of treatment with opioids.
Acetaminophen; Pamabrom; Pyrilamine: (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of other sedating medications, such as sedating H1-blockers.
Acetaminophen; Pentazocine: (Contraindicated) Concomitant use of safinamide with opioids is contraindicated due to the risk of serotonin syndrome. Allow at least 14 days between discontinuation of safinamide and initiation of treatment with opioids.
Acetaminophen; Pseudoephedrine: (Moderate) Severe hypertensive reactions, including hypertensive crisis, have been reported in patients taking monoamine oxidase inhibitors (MAOIs), such as safinamide concurrently with sympathomimetic medications, such as pseudoephedrine. If concomitant use of safinamide and pseudoephedrine is necessary, monitor for hypertension and hypertensive crisis.
Acrivastine; Pseudoephedrine: (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of other sedating medications, such as sedating H1-blockers. (Moderate) Severe hypertensive reactions, including hypertensive crisis, have been reported in patients taking monoamine oxidase inhibitors (MAOIs), such as safinamide concurrently with sympathomimetic medications, such as pseudoephedrine. If concomitant use of safinamide and pseudoephedrine is necessary, monitor for hypertension and hypertensive crisis.
Alfentanil: (Contraindicated) Concomitant use of safinamide with opioids is contraindicated due to the risk of serotonin syndrome. Allow at least 14 days between discontinuation of safinamide and initiation of treatment with opioids.
Almotriptan: (Moderate) Safinamide and serotonin-receptor agonists, also known as triptans, should be used together with caution. Serotonin syndrome has been reported during administration of serotonin-receptor agonists and non-selective monoamine oxidase inhibitors (MAOIs). Since safinamide selectively inhibits MAO-B at recommended doses, no interaction with serotonin-receptor agonists would be expected with normal prescription use. However, monitoring for serotonin-related side effects is advisable since the potential for serotonin syndrome exists. If serotonin syndrome occurs, discontinue all serotonergic agents and institute appropriate treatment.
Alpelisib: (Major) Avoid coadministration of alpelisib with safinamide due to increased exposure to alpelisib and the risk of alpelisib-related toxicity. If concomitant use is unavoidable, closely monitor for alpelisib-related adverse reactions. Alpelisib is a BCRP substrate and safinamide is a BCRP inhibitor.
Alprazolam: (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of safinamide with other sedating medications, such as benzodiazepines.
Amitriptyline: (Contraindicated) Safinamide is contraindicated for use with tricyclic antidepressants (TCAs) due to the risk of serotonin syndrome. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. At least 14 days should elapse between the discontinuation of safinamide and the initiation of a TCA.
Amobarbital: (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of safinamide with other sedating medications, such as barbiturates.
Amoxapine: (Contraindicated) Safinamide is contraindicated for use with amoxapine due to the risk of serotonin syndrome. At least 14 days should elapse between the discontinuation of safinamide and the initiation of amoxapine.
Amphetamine: (Contraindicated) Safinamide, a selective monoamine oxidase-B inhibitor, is contraindicated for use with amphetamines due to the risk of serotonin syndrome or hypertensive crisis. The manufacturer of safinamide recommends that a period of at least 14 days elapse between the discontinuation of safinamide and the initiation of serotonergic agents. Hypertensive crisis has been reported in patients taking recommended doses of selective MAO-B inhibitors and sympathomimetic medications, such as amphetamines. Safinamide can cause hypertension or exacerbate existing hypertension, particularly at daily dosages exceeding those recommended by the manufacturer.
Amphetamine; Dextroamphetamine: (Contraindicated) Safinamide, a selective monoamine oxidase-B inhibitor, is contraindicated for use with amphetamines due to the risk of serotonin syndrome or hypertensive crisis. The manufacturer of safinamide recommends that a period of at least 14 days elapse between the discontinuation of safinamide and the initiation of serotonergic agents. Hypertensive crisis has been reported in patients taking recommended doses of selective MAO-B inhibitors and sympathomimetic medications, such as amphetamines. Safinamide can cause hypertension or exacerbate existing hypertension, particularly at daily dosages exceeding those recommended by the manufacturer.
Amphetamines: (Contraindicated) Safinamide, a selective monoamine oxidase-B inhibitor, is contraindicated for use with amphetamines due to the risk of serotonin syndrome or hypertensive crisis. The manufacturer of safinamide recommends that a period of at least 14 days elapse between the discontinuation of safinamide and the initiation of serotonergic agents. Hypertensive crisis has been reported in patients taking recommended doses of selective MAO-B inhibitors and sympathomimetic medications, such as amphetamines. Safinamide can cause hypertension or exacerbate existing hypertension, particularly at daily dosages exceeding those recommended by the manufacturer.
Anxiolytics; Sedatives; and Hypnotics: (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of safinamide with other sedating medications, such as anxiolytics, sedatives, and hypnotics.
Aripiprazole: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or safinamide during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and safinamide may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with safinamide than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
Articaine; Epinephrine: (Moderate) Severe hypertensive reactions, including hypertensive crisis, have been reported in patients taking monoamine oxidase inhibitors (MAOIs), such as safinamide, and sympathomimetic medications, such as epinephrine. If concomitant use of safinamide and epinephrine is necessary, monitor for hypertension and hypertensive crisis.
Asenapine: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or safinamide during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and safinamide may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with safinamide than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
Aspirin, ASA; Butalbital; Caffeine: (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of safinamide with other sedating medications, such as barbiturates.
Aspirin, ASA; Butalbital; Caffeine; Codeine: (Contraindicated) Concomitant use of safinamide with opioids is contraindicated due to the risk of serotonin syndrome. Allow at least 14 days between discontinuation of safinamide and initiation of treatment with opioids. (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of safinamide with other sedating medications, such as barbiturates.
Aspirin, ASA; Carisoprodol; Codeine: (Contraindicated) Concomitant use of safinamide with opioids is contraindicated due to the risk of serotonin syndrome. Allow at least 14 days between discontinuation of safinamide and initiation of treatment with opioids.
Aspirin, ASA; Oxycodone: (Contraindicated) Concomitant use of safinamide with opioids is contraindicated due to the risk of serotonin syndrome. Allow at least 14 days between discontinuation of safinamide and initiation of treatment with opioids.
Atomoxetine: (Contraindicated) The use of selective norepinephrine reuptake inhibitors (such as atomoxetine) with monoamine oxidase inhibitors (MAOIs) is contraindicated. At least 2 weeks should elapse between the discontinuation of a drug with MAO inhibiting activity and the start of selective norepinephrine reuptake inhibitors, or vice-versa. Selective norepinephrine reuptake inhibitors potentiate certain catecholamines by inhibiting neuronal reuptake. Reactions with MAOIs may include confusion, seizures, and severe hypertension as well as less severe symptoms.
Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Major) Concurrent use of intravenous (IV) methylene blue and MAOIs such as safinamide should generally be avoided due to the potential for serotonin syndrome. If emergent treatment with methylene blue is required in a patient receiving an MAOI it is advisable to discontinue the MAOI and monitor the patient for symptoms of CNS toxicity for two weeks or until 24 hours after the last dose of methylene blue, whichever comes first. During non-emergent use of methylene blue, it is advisable to discontinue the MAOI at least 2 weeks prior to methylene blue treatment, but also taking into consideration the half-life of the MAOI being discontinued. Because safinamide is a selective monoamine oxidase-B (MAO-B) inhibitor at manufacturer recommended doses, an interaction may be less likely to occur than with other traditional MAOIs. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A). Cases of serotonin syndrome have been reported, primarily following administration of IV methylene blue (1 to 8 mg/kg) as a visualizing agent in patients receiving serotonergic agents.
atypical antipsychotic: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or safinamide during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and safinamide may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with safinamide than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
Barbiturates: (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of safinamide with other sedating medications, such as barbiturates.
Belladonna; Opium: (Contraindicated) Concomitant use of safinamide with opioids is contraindicated due to the risk of serotonin syndrome. Allow at least 14 days between discontinuation of safinamide and initiation of treatment with opioids.
Benzhydrocodone; Acetaminophen: (Contraindicated) Concomitant use of safinamide with opioids is contraindicated due to the risk of serotonin syndrome. Allow at least 14 days between discontinuation of safinamide and initiation of treatment with opioids.
Benzodiazepines: (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of safinamide with other sedating medications, such as benzodiazepines.
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Major) Concurrent use of intravenous (IV) methylene blue and MAOIs such as safinamide should generally be avoided due to the potential for serotonin syndrome. If emergent treatment with methylene blue is required in a patient receiving an MAOI it is advisable to discontinue the MAOI and monitor the patient for symptoms of CNS toxicity for two weeks or until 24 hours after the last dose of methylene blue, whichever comes first. During non-emergent use of methylene blue, it is advisable to discontinue the MAOI at least 2 weeks prior to methylene blue treatment, but also taking into consideration the half-life of the MAOI being discontinued. Because safinamide is a selective monoamine oxidase-B (MAO-B) inhibitor at manufacturer recommended doses, an interaction may be less likely to occur than with other traditional MAOIs. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A). Cases of serotonin syndrome have been reported, primarily following administration of IV methylene blue (1 to 8 mg/kg) as a visualizing agent in patients receiving serotonergic agents.
Benzphetamine: (Contraindicated) Safinamide, a selective monoamine oxidase-B inhibitor, is contraindicated for use with amphetamines due to the risk of serotonin syndrome or hypertensive crisis. The manufacturer of safinamide recommends that a period of at least 14 days elapse between the discontinuation of safinamide and the initiation of serotonergic agents. Hypertensive crisis has been reported in patients taking recommended doses of selective MAO-B inhibitors and sympathomimetic medications, such as amphetamines. Safinamide can cause hypertension or exacerbate existing hypertension, particularly at daily dosages exceeding those recommended by the manufacturer.
Berotralstat: (Major) Reduce the berotralstat dose to 110 mg PO once daily in patients chronically taking safinamide. Concurrent use may increase berotralstat exposure and the risk of adverse effects. Berotralstat is a BCRP substrate and safinamide is a BCRP inhibitor. Coadministration with another BCRP inhibitor increased berotralstat exposure by 69%.
Brexpiprazole: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or safinamide during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and safinamide may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with safinamide than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
Brompheniramine: (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of other sedating medications, such as sedating H1-blockers.
Brompheniramine; Dextromethorphan; Guaifenesin: (Contraindicated) Dextromethorphan prescription products are contraindicated in patients taking monoamine oxidase inhibitors (MAOIs) or in patients who have taken MAOIs within the preceding 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. Allow at least 14 days after stopping dextromethorphan before starting an MAOI, including safinamide. Brief episodes of psychosis or bizarre behavior have also been reported with this combination. Patients should read nonprescription product labels carefully. Before initiating an MAOI after using other serotoninergic agents, a sufficient amount of time must be allowed for clearance of the serotoninergic agent and its active metabolites. (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of other sedating medications, such as sedating H1-blockers.
Brompheniramine; Dextromethorphan; Phenylephrine: (Contraindicated) Dextromethorphan prescription products are contraindicated in patients taking monoamine oxidase inhibitors (MAOIs) or in patients who have taken MAOIs within the preceding 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. Allow at least 14 days after stopping dextromethorphan before starting an MAOI, including safinamide. Brief episodes of psychosis or bizarre behavior have also been reported with this combination. Patients should read nonprescription product labels carefully. Before initiating an MAOI after using other serotoninergic agents, a sufficient amount of time must be allowed for clearance of the serotoninergic agent and its active metabolites. (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of other sedating medications, such as sedating H1-blockers. (Moderate) Severe hypertensive reactions, including hypertensive crisis, have been reported in patients taking monoamine oxidase inhibitors (MAOIs), such as safinamide, and sympathomimetic medications, such as phenylephrine. If concomitant use of safinamide and phenylephrine is necessary, monitor for hypertension and hypertensive crisis.
Brompheniramine; Phenylephrine: (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of other sedating medications, such as sedating H1-blockers. (Moderate) Severe hypertensive reactions, including hypertensive crisis, have been reported in patients taking monoamine oxidase inhibitors (MAOIs), such as safinamide, and sympathomimetic medications, such as phenylephrine. If concomitant use of safinamide and phenylephrine is necessary, monitor for hypertension and hypertensive crisis.
Brompheniramine; Pseudoephedrine: (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of other sedating medications, such as sedating H1-blockers. (Moderate) Severe hypertensive reactions, including hypertensive crisis, have been reported in patients taking monoamine oxidase inhibitors (MAOIs), such as safinamide concurrently with sympathomimetic medications, such as pseudoephedrine. If concomitant use of safinamide and pseudoephedrine is necessary, monitor for hypertension and hypertensive crisis.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Contraindicated) Dextromethorphan prescription products are contraindicated in patients taking monoamine oxidase inhibitors (MAOIs) or in patients who have taken MAOIs within the preceding 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. Allow at least 14 days after stopping dextromethorphan before starting an MAOI, including safinamide. Brief episodes of psychosis or bizarre behavior have also been reported with this combination. Patients should read nonprescription product labels carefully. Before initiating an MAOI after using other serotoninergic agents, a sufficient amount of time must be allowed for clearance of the serotoninergic agent and its active metabolites. (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of other sedating medications, such as sedating H1-blockers. (Moderate) Severe hypertensive reactions, including hypertensive crisis, have been reported in patients taking monoamine oxidase inhibitors (MAOIs), such as safinamide concurrently with sympathomimetic medications, such as pseudoephedrine. If concomitant use of safinamide and pseudoephedrine is necessary, monitor for hypertension and hypertensive crisis.
Bupivacaine; Epinephrine: (Moderate) Severe hypertensive reactions, including hypertensive crisis, have been reported in patients taking monoamine oxidase inhibitors (MAOIs), such as safinamide, and sympathomimetic medications, such as epinephrine. If concomitant use of safinamide and epinephrine is necessary, monitor for hypertension and hypertensive crisis.
Buprenorphine: (Contraindicated) Concomitant use of safinamide with opioids is contraindicated due to the risk of serotonin syndrome. Allow at least 14 days between discontinuation of safinamide and initiation of treatment with opioids.
Buprenorphine; Naloxone: (Contraindicated) Concomitant use of safinamide with opioids is contraindicated due to the risk of serotonin syndrome. Allow at least 14 days between discontinuation of safinamide and initiation of treatment with opioids.
Butabarbital: (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of safinamide with other sedating medications, such as barbiturates.
Butalbital; Acetaminophen: (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of safinamide with other sedating medications, such as barbiturates.
Butalbital; Acetaminophen; Caffeine: (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of safinamide with other sedating medications, such as barbiturates.
Butalbital; Acetaminophen; Caffeine; Codeine: (Contraindicated) Concomitant use of safinamide with opioids is contraindicated due to the risk of serotonin syndrome. Allow at least 14 days between discontinuation of safinamide and initiation of treatment with opioids. (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of safinamide with other sedating medications, such as barbiturates.
Butorphanol: (Contraindicated) Concomitant use of safinamide with opioids is contraindicated due to the risk of serotonin syndrome. Allow at least 14 days between discontinuation of safinamide and initiation of treatment with opioids.
Carbidopa; Levodopa: (Moderate) Safinamide and carbidopa; levodopa are indicated for use in combination; however, there is the possibility of new onset dyskinesias or exacerbation of pre-existing dyskinesias. Patients should be advised to contact their health care provider if they notice new or worsening dyskinesias while taking these medicines together.
Carbidopa; Levodopa; Entacapone: (Moderate) Safinamide and carbidopa; levodopa are indicated for use in combination; however, there is the possibility of new onset dyskinesias or exacerbation of pre-existing dyskinesias. Patients should be advised to contact their health care provider if they notice new or worsening dyskinesias while taking these medicines together.
Carbinoxamine: (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of other sedating medications, such as sedating H1-blockers.
Carbinoxamine; Dextromethorphan; Pseudoephedrine: (Contraindicated) Dextromethorphan prescription products are contraindicated in patients taking monoamine oxidase inhibitors (MAOIs) or in patients who have taken MAOIs within the preceding 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. Allow at least 14 days after stopping dextromethorphan before starting an MAOI, including safinamide. Brief episodes of psychosis or bizarre behavior have also been reported with this combination. Patients should read nonprescription product labels carefully. Before initiating an MAOI after using other serotoninergic agents, a sufficient amount of time must be allowed for clearance of the serotoninergic agent and its active metabolites. (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of other sedating medications, such as sedating H1-blockers. (Moderate) Severe hypertensive reactions, including hypertensive crisis, have been reported in patients taking monoamine oxidase inhibitors (MAOIs), such as safinamide concurrently with sympathomimetic medications, such as pseudoephedrine. If concomitant use of safinamide and pseudoephedrine is necessary, monitor for hypertension and hypertensive crisis.
Carbinoxamine; Phenylephrine: (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of other sedating medications, such as sedating H1-blockers. (Moderate) Severe hypertensive reactions, including hypertensive crisis, have been reported in patients taking monoamine oxidase inhibitors (MAOIs), such as safinamide, and sympathomimetic medications, such as phenylephrine. If concomitant use of safinamide and phenylephrine is necessary, monitor for hypertension and hypertensive crisis.
Carbinoxamine; Pseudoephedrine: (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of other sedating medications, such as sedating H1-blockers. (Moderate) Severe hypertensive reactions, including hypertensive crisis, have been reported in patients taking monoamine oxidase inhibitors (MAOIs), such as safinamide concurrently with sympathomimetic medications, such as pseudoephedrine. If concomitant use of safinamide and pseudoephedrine is necessary, monitor for hypertension and hypertensive crisis.
Cariprazine: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or safinamide during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and safinamide may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with safinamide than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
Celecoxib; Tramadol: (Contraindicated) Concomitant use of safinamide with opioids is contraindicated due to the risk of serotonin syndrome. Allow at least 14 days between discontinuation of safinamide and initiation of treatment with opioids.
Cenobamate: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cenobamate and safinamide. Concurrent use may result in additive CNS depression. Dopaminergic agents, such as safinamide, have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Cetirizine: (Moderate) Concurrent use of cetirizine/levocetirizine with safinamide should generally be avoided because of the possibility of additive sedative effects. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Cetirizine; Pseudoephedrine: (Moderate) Concurrent use of cetirizine/levocetirizine with safinamide should generally be avoided because of the possibility of additive sedative effects. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. (Moderate) Severe hypertensive reactions, including hypertensive crisis, have been reported in patients taking monoamine oxidase inhibitors (MAOIs), such as safinamide concurrently with sympathomimetic medications, such as pseudoephedrine. If concomitant use of safinamide and pseudoephedrine is necessary, monitor for hypertension and hypertensive crisis.
Chlophedianol; Dexbrompheniramine: (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of other sedating medications, such as sedating H1-blockers.
Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of other sedating medications, such as sedating H1-blockers. (Moderate) Severe hypertensive reactions, including hypertensive crisis, have been reported in patients taking monoamine oxidase inhibitors (MAOIs), such as safinamide concurrently with sympathomimetic medications, such as pseudoephedrine. If concomitant use of safinamide and pseudoephedrine is necessary, monitor for hypertension and hypertensive crisis.
Chlorcyclizine: (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of other sedating medications, such as sedating H1-blockers.
Chlordiazepoxide: (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of safinamide with other sedating medications, such as benzodiazepines.
Chlordiazepoxide; Amitriptyline: (Contraindicated) Safinamide is contraindicated for use with tricyclic antidepressants (TCAs) due to the risk of serotonin syndrome. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. At least 14 days should elapse between the discontinuation of safinamide and the initiation of a TCA. (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of safinamide with other sedating medications, such as benzodiazepines.
Chlordiazepoxide; Clidinium: (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of safinamide with other sedating medications, such as benzodiazepines.
Chlorpheniramine: (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of other sedating medications, such as sedating H1-blockers.
Chlorpheniramine; Codeine: (Contraindicated) Concomitant use of safinamide with opioids is contraindicated due to the risk of serotonin syndrome. Allow at least 14 days between discontinuation of safinamide and initiation of treatment with opioids. (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of other sedating medications, such as sedating H1-blockers.
Chlorpheniramine; Dextromethorphan: (Contraindicated) Dextromethorphan prescription products are contraindicated in patients taking monoamine oxidase inhibitors (MAOIs) or in patients who have taken MAOIs within the preceding 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. Allow at least 14 days after stopping dextromethorphan before starting an MAOI, including safinamide. Brief episodes of psychosis or bizarre behavior have also been reported with this combination. Patients should read nonprescription product labels carefully. Before initiating an MAOI after using other serotoninergic agents, a sufficient amount of time must be allowed for clearance of the serotoninergic agent and its active metabolites. (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of other sedating medications, such as sedating H1-blockers.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Contraindicated) Dextromethorphan prescription products are contraindicated in patients taking monoamine oxidase inhibitors (MAOIs) or in patients who have taken MAOIs within the preceding 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. Allow at least 14 days after stopping dextromethorphan before starting an MAOI, including safinamide. Brief episodes of psychosis or bizarre behavior have also been reported with this combination. Patients should read nonprescription product labels carefully. Before initiating an MAOI after using other serotoninergic agents, a sufficient amount of time must be allowed for clearance of the serotoninergic agent and its active metabolites. (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of other sedating medications, such as sedating H1-blockers. (Moderate) Severe hypertensive reactions, including hypertensive crisis, have been reported in patients taking monoamine oxidase inhibitors (MAOIs), such as safinamide, and sympathomimetic medications, such as phenylephrine. If concomitant use of safinamide and phenylephrine is necessary, monitor for hypertension and hypertensive crisis.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Contraindicated) Dextromethorphan prescription products are contraindicated in patients taking monoamine oxidase inhibitors (MAOIs) or in patients who have taken MAOIs within the preceding 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. Allow at least 14 days after stopping dextromethorphan before starting an MAOI, including safinamide. Brief episodes of psychosis or bizarre behavior have also been reported with this combination. Patients should read nonprescription product labels carefully. Before initiating an MAOI after using other serotoninergic agents, a sufficient amount of time must be allowed for clearance of the serotoninergic agent and its active metabolites. (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of other sedating medications, such as sedating H1-blockers. (Moderate) Severe hypertensive reactions, including hypertensive crisis, have been reported in patients taking monoamine oxidase inhibitors (MAOIs), such as safinamide concurrently with sympathomimetic medications, such as pseudoephedrine. If concomitant use of safinamide and pseudoephedrine is necessary, monitor for hypertension and hypertensive crisis.
Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Contraindicated) Concomitant use of safinamide with opioids is contraindicated due to the risk of serotonin syndrome. Allow at least 14 days between discontinuation of safinamide and initiation of treatment with opioids. (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of other sedating medications, such as sedating H1-blockers. (Moderate) Severe hypertensive reactions, including hypertensive crisis, have been reported in patients taking monoamine oxidase inhibitors (MAOIs), such as safinamide, and sympathomimetic medications, such as phenylephrine. If concomitant use of safinamide and phenylephrine is necessary, monitor for hypertension and hypertensive crisis.
Chlorpheniramine; Hydrocodone: (Contraindicated) Concomitant use of safinamide with opioids is contraindicated due to the risk of serotonin syndrome. Allow at least 14 days between discontinuation of safinamide and initiation of treatment with opioids. (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of other sedating medications, such as sedating H1-blockers.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of other sedating medications, such as sedating H1-blockers. (Moderate) Severe hypertensive reactions, including hypertensive crisis, have been reported in patients taking monoamine oxidase inhibitors (MAOIs), such as safinamide concurrently with sympathomimetic medications, such as pseudoephedrine. If concomitant use of safinamide and pseudoephedrine is necessary, monitor for hypertension and hypertensive crisis.
Chlorpheniramine; Phenylephrine: (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of other sedating medications, such as sedating H1-blockers. (Moderate) Severe hypertensive reactions, including hypertensive crisis, have been reported in patients taking monoamine oxidase inhibitors (MAOIs), such as safinamide, and sympathomimetic medications, such as phenylephrine. If concomitant use of safinamide and phenylephrine is necessary, monitor for hypertension and hypertensive crisis.
Chlorpheniramine; Pseudoephedrine: (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of other sedating medications, such as sedating H1-blockers. (Moderate) Severe hypertensive reactions, including hypertensive crisis, have been reported in patients taking monoamine oxidase inhibitors (MAOIs), such as safinamide concurrently with sympathomimetic medications, such as pseudoephedrine. If concomitant use of safinamide and pseudoephedrine is necessary, monitor for hypertension and hypertensive crisis.
Chlorpromazine: (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and safinamide may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine if appropriate. If coadministration cannot be avoided, monitor for changes in movements, moods, or behaviors.
Citalopram: (Major) The concurrent use of selective serotonin reuptake inhibitors (SSRIs) and monoamine oxidase inhibitors (MAOIs) is generally avoided; however, the manufacturer of safinamide recommends monitoring for serotonin syndrome and using the lowest effective dose of the SSRI during concurrent use. During clinical trial evaluation of safinamide, 1 case of serotonin syndrome occurred during co-administration with an SSRI. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death.
Clemastine: (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of other sedating medications, such as sedating H1-blockers.
Clomipramine: (Contraindicated) Safinamide is contraindicated for use with tricyclic antidepressants (TCAs) due to the risk of serotonin syndrome. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. At least 14 days should elapse between the discontinuation of safinamide and the initiation of a TCA.
Clonazepam: (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of safinamide with other sedating medications, such as benzodiazepines.
Clorazepate: (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of safinamide with other sedating medications, such as benzodiazepines.
Clozapine: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or safinamide during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and safinamide may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with safinamide than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
Codeine: (Contraindicated) Concomitant use of safinamide with opioids is contraindicated due to the risk of serotonin syndrome. Allow at least 14 days between discontinuation of safinamide and initiation of treatment with opioids.
Codeine; Guaifenesin: (Contraindicated) Concomitant use of safinamide with opioids is contraindicated due to the risk of serotonin syndrome. Allow at least 14 days between discontinuation of safinamide and initiation of treatment with opioids.
Codeine; Guaifenesin; Pseudoephedrine: (Contraindicated) Concomitant use of safinamide with opioids is contraindicated due to the risk of serotonin syndrome. Allow at least 14 days between discontinuation of safinamide and initiation of treatment with opioids. (Moderate) Severe hypertensive reactions, including hypertensive crisis, have been reported in patients taking monoamine oxidase inhibitors (MAOIs), such as safinamide concurrently with sympathomimetic medications, such as pseudoephedrine. If concomitant use of safinamide and pseudoephedrine is necessary, monitor for hypertension and hypertensive crisis.
Codeine; Phenylephrine; Promethazine: (Contraindicated) Concomitant use of safinamide with opioids is contraindicated due to the risk of serotonin syndrome. Allow at least 14 days between discontinuation of safinamide and initiation of treatment with opioids. (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and safinamide may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine if appropriate. If coadministration cannot be avoided, monitor for changes in movements, moods, or behaviors. (Moderate) Severe hypertensive reactions, including hypertensive crisis, have been reported in patients taking monoamine oxidase inhibitors (MAOIs), such as safinamide, and sympathomimetic medications, such as phenylephrine. If concomitant use of safinamide and phenylephrine is necessary, monitor for hypertension and hypertensive crisis.
Codeine; Promethazine: (Contraindicated) Concomitant use of safinamide with opioids is contraindicated due to the risk of serotonin syndrome. Allow at least 14 days between discontinuation of safinamide and initiation of treatment with opioids. (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and safinamide may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine if appropriate. If coadministration cannot be avoided, monitor for changes in movements, moods, or behaviors.
Cyclizine: (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of other sedating medications, such as sedating H1-blockers.
Cyclobenzaprine: (Contraindicated) Safinamide is contraindicated for use with cyclobenzaprine due to the risk of serotonin syndrome. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. At least 14 days should elapse between the discontinuation of safinamide and the initiation of cyclobenzaprine.
Cyproheptadine: (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of other sedating medications, such as sedating H1-blockers.
Desipramine: (Contraindicated) Safinamide is contraindicated for use with tricyclic antidepressants (TCAs) due to the risk of serotonin syndrome. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. At least 14 days should elapse between the discontinuation of safinamide and the initiation of a TCA.
Desloratadine; Pseudoephedrine: (Moderate) Severe hypertensive reactions, including hypertensive crisis, have been reported in patients taking monoamine oxidase inhibitors (MAOIs), such as safinamide concurrently with sympathomimetic medications, such as pseudoephedrine. If concomitant use of safinamide and pseudoephedrine is necessary, monitor for hypertension and hypertensive crisis.
Desvenlafaxine: (Contraindicated) Safinamide is contraindicated for use with serotonin norepinephrine reuptake inhibitors (SNRIs) due to the risk of serotonin syndrome. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. At least 14 days should elapse between the discontinuation of safinamide and the initiation of an SNRI.
Deutetrabenazine: (Contraindicated) Deutetrabenazine use is contraindicated in patients who are receiving or have received MAOI therapy within the past 14 days. The major metabolites of deutetrabenazine (alpha-dihydrotetrabenazine [HTBZ] and beta-HTBZ) are reversible inhibitors of vesicular monoamine transporter 2 (VMAT2). Inhibition of VMAT2 results in decreased uptake of monoamines into synaptic vesicles and depletion of monoamine stores.
Dexbrompheniramine: (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of other sedating medications, such as sedating H1-blockers.
Dexbrompheniramine; Pseudoephedrine: (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of other sedating medications, such as sedating H1-blockers. (Moderate) Severe hypertensive reactions, including hypertensive crisis, have been reported in patients taking monoamine oxidase inhibitors (MAOIs), such as safinamide concurrently with sympathomimetic medications, such as pseudoephedrine. If concomitant use of safinamide and pseudoephedrine is necessary, monitor for hypertension and hypertensive crisis.
Dexchlorpheniramine: (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of other sedating medications, such as sedating H1-blockers.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Contraindicated) Dextromethorphan prescription products are contraindicated in patients taking monoamine oxidase inhibitors (MAOIs) or in patients who have taken MAOIs within the preceding 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. Allow at least 14 days after stopping dextromethorphan before starting an MAOI, including safinamide. Brief episodes of psychosis or bizarre behavior have also been reported with this combination. Patients should read nonprescription product labels carefully. Before initiating an MAOI after using other serotoninergic agents, a sufficient amount of time must be allowed for clearance of the serotoninergic agent and its active metabolites. (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of other sedating medications, such as sedating H1-blockers. (Moderate) Severe hypertensive reactions, including hypertensive crisis, have been reported in patients taking monoamine oxidase inhibitors (MAOIs), such as safinamide concurrently with sympathomimetic medications, such as pseudoephedrine. If concomitant use of safinamide and pseudoephedrine is necessary, monitor for hypertension and hypertensive crisis.
Dextroamphetamine: (Contraindicated) Safinamide, a selective monoamine oxidase-B inhibitor, is contraindicated for use with amphetamines due to the risk of serotonin syndrome or hypertensive crisis. The manufacturer of safinamide recommends that a period of at least 14 days elapse between the discontinuation of safinamide and the initiation of serotonergic agents. Hypertensive crisis has been reported in patients taking recommended doses of selective MAO-B inhibitors and sympathomimetic medications, such as amphetamines. Safinamide can cause hypertension or exacerbate existing hypertension, particularly at daily dosages exceeding those recommended by the manufacturer.
Dextromethorphan: (Contraindicated) Dextromethorphan prescription products are contraindicated in patients taking monoamine oxidase inhibitors (MAOIs) or in patients who have taken MAOIs within the preceding 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. Allow at least 14 days after stopping dextromethorphan before starting an MAOI, including safinamide. Brief episodes of psychosis or bizarre behavior have also been reported with this combination. Patients should read nonprescription product labels carefully. Before initiating an MAOI after using other serotoninergic agents, a sufficient amount of time must be allowed for clearance of the serotoninergic agent and its active metabolites.
Dextromethorphan; Bupropion: (Contraindicated) Dextromethorphan prescription products are contraindicated in patients taking monoamine oxidase inhibitors (MAOIs) or in patients who have taken MAOIs within the preceding 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. Allow at least 14 days after stopping dextromethorphan before starting an MAOI, including safinamide. Brief episodes of psychosis or bizarre behavior have also been reported with this combination. Patients should read nonprescription product labels carefully. Before initiating an MAOI after using other serotoninergic agents, a sufficient amount of time must be allowed for clearance of the serotoninergic agent and its active metabolites.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Contraindicated) Dextromethorphan prescription products are contraindicated in patients taking monoamine oxidase inhibitors (MAOIs) or in patients who have taken MAOIs within the preceding 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. Allow at least 14 days after stopping dextromethorphan before starting an MAOI, including safinamide. Brief episodes of psychosis or bizarre behavior have also been reported with this combination. Patients should read nonprescription product labels carefully. Before initiating an MAOI after using other serotoninergic agents, a sufficient amount of time must be allowed for clearance of the serotoninergic agent and its active metabolites. (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of other sedating medications, such as sedating H1-blockers. (Moderate) Severe hypertensive reactions, including hypertensive crisis, have been reported in patients taking monoamine oxidase inhibitors (MAOIs), such as safinamide, and sympathomimetic medications, such as phenylephrine. If concomitant use of safinamide and phenylephrine is necessary, monitor for hypertension and hypertensive crisis.
Dextromethorphan; Guaifenesin: (Contraindicated) Dextromethorphan prescription products are contraindicated in patients taking monoamine oxidase inhibitors (MAOIs) or in patients who have taken MAOIs within the preceding 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. Allow at least 14 days after stopping dextromethorphan before starting an MAOI, including safinamide. Brief episodes of psychosis or bizarre behavior have also been reported with this combination. Patients should read nonprescription product labels carefully. Before initiating an MAOI after using other serotoninergic agents, a sufficient amount of time must be allowed for clearance of the serotoninergic agent and its active metabolites.
Dextromethorphan; Guaifenesin; Phenylephrine: (Contraindicated) Dextromethorphan prescription products are contraindicated in patients taking monoamine oxidase inhibitors (MAOIs) or in patients who have taken MAOIs within the preceding 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. Allow at least 14 days after stopping dextromethorphan before starting an MAOI, including safinamide. Brief episodes of psychosis or bizarre behavior have also been reported with this combination. Patients should read nonprescription product labels carefully. Before initiating an MAOI after using other serotoninergic agents, a sufficient amount of time must be allowed for clearance of the serotoninergic agent and its active metabolites. (Moderate) Severe hypertensive reactions, including hypertensive crisis, have been reported in patients taking monoamine oxidase inhibitors (MAOIs), such as safinamide, and sympathomimetic medications, such as phenylephrine. If concomitant use of safinamide and phenylephrine is necessary, monitor for hypertension and hypertensive crisis.
Dextromethorphan; Guaifenesin; Potassium Guaiacolsulfonate: (Contraindicated) Dextromethorphan prescription products are contraindicated in patients taking monoamine oxidase inhibitors (MAOIs) or in patients who have taken MAOIs within the preceding 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. Allow at least 14 days after stopping dextromethorphan before starting an MAOI, including safinamide. Brief episodes of psychosis or bizarre behavior have also been reported with this combination. Patients should read nonprescription product labels carefully. Before initiating an MAOI after using other serotoninergic agents, a sufficient amount of time must be allowed for clearance of the serotoninergic agent and its active metabolites.
Dextromethorphan; Guaifenesin; Pseudoephedrine: (Contraindicated) Dextromethorphan prescription products are contraindicated in patients taking monoamine oxidase inhibitors (MAOIs) or in patients who have taken MAOIs within the preceding 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. Allow at least 14 days after stopping dextromethorphan before starting an MAOI, including safinamide. Brief episodes of psychosis or bizarre behavior have also been reported with this combination. Patients should read nonprescription product labels carefully. Before initiating an MAOI after using other serotoninergic agents, a sufficient amount of time must be allowed for clearance of the serotoninergic agent and its active metabolites. (Moderate) Severe hypertensive reactions, including hypertensive crisis, have been reported in patients taking monoamine oxidase inhibitors (MAOIs), such as safinamide concurrently with sympathomimetic medications, such as pseudoephedrine. If concomitant use of safinamide and pseudoephedrine is necessary, monitor for hypertension and hypertensive crisis.
Dextromethorphan; Quinidine: (Contraindicated) Dextromethorphan prescription products are contraindicated in patients taking monoamine oxidase inhibitors (MAOIs) or in patients who have taken MAOIs within the preceding 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. Allow at least 14 days after stopping dextromethorphan before starting an MAOI, including safinamide. Brief episodes of psychosis or bizarre behavior have also been reported with this combination. Patients should read nonprescription product labels carefully. Before initiating an MAOI after using other serotoninergic agents, a sufficient amount of time must be allowed for clearance of the serotoninergic agent and its active metabolites.
Diazepam: (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of safinamide with other sedating medications, such as benzodiazepines.
Diethylpropion: (Moderate) Severe hypertensive reactions, including hypertensive crisis, have been reported in patients taking monoamine oxidase inhibitors (MAOIs), such as safinamide, and sympathomimetic medications, such as diethylpropion. If concomitant use of safinamide and diethylpropion is necessary, monitor for hypertension and hypertensive crisis.
Difelikefalin: (Moderate) Monitor for dizziness, somnolence, mental status changes, and gait disturbances if concomitant use of difelikefalin with CNS depressants is necessary. Concomitant use may increase the risk for these adverse reactions.
Dimenhydrinate: (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of other sedating medications, such as sedating H1-blockers.
Diphenhydramine: (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of other sedating medications, such as sedating H1-blockers.
Diphenhydramine; Ibuprofen: (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of other sedating medications, such as sedating H1-blockers.
Diphenhydramine; Naproxen: (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of other sedating medications, such as sedating H1-blockers.
Diphenhydramine; Phenylephrine: (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of other sedating medications, such as sedating H1-blockers. (Moderate) Severe hypertensive reactions, including hypertensive crisis, have been reported in patients taking monoamine oxidase inhibitors (MAOIs), such as safinamide, and sympathomimetic medications, such as phenylephrine. If concomitant use of safinamide and phenylephrine is necessary, monitor for hypertension and hypertensive crisis.
Dobutamine: (Moderate) Severe hypertensive reactions, including hypertensive crisis, have been reported in patients taking monoamine oxidase inhibitors (MAOIs), such as safinamide, and sympathomimetic medications, such as dobutamine. Because dobutamine is only administered in a hospital or medical facility, your health care provider will monitor you for hypertensive reactions while you are receiving safinamide and dobutamine together.
Dopamine: (Moderate) Severe hypertensive reactions, including hypertensive crisis, have been reported in patients taking monoamine oxidase inhibitors (MAOIs), such as safinamide, and sympathomimetic medications, such as dopamine. If concomitant use of safinamide and dopamine is necessary, monitor for hypertension and hypertensive crisis.
Doxapram: (Moderate) Severe hypertensive reactions, including hypertensive crisis, have been reported in patients taking monoamine oxidase inhibitors (MAOIs), such as safinamide, and sympathomimetic medications, such as doxapram. If concomitant use of safinamide and doxapram is necessary, monitor for hypertension and hypertensive crisis.
Doxepin: (Contraindicated) Safinamide is contraindicated for use with tricyclic antidepressants (TCAs) due to the risk of serotonin syndrome. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. At least 14 days should elapse between the discontinuation of safinamide and the initiation of a TCA.
Doxylamine: (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of other sedating medications, such as sedating H1-blockers.
Doxylamine; Pyridoxine: (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of other sedating medications, such as sedating H1-blockers.
Droperidol: (Major) The concurrent use of safinamide and droperidol should be avoided if possible. The beneficial effects of safinamide are mediated by monoamine oxidase inhibitor type B activity which increases central dopamine availability and droperidol is a dopamine antagonist. If these agents must be used together, monitor for exacerbation of Parkinson's disease symptoms.
Duloxetine: (Contraindicated) Safinamide is contraindicated for use with serotonin norepinephrine reuptake inhibitors (SNRIs) due to the risk of serotonin syndrome. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. At least 14 days should elapse between the discontinuation of safinamide and the initiation of an SNRI.
Eletriptan: (Moderate) Safinamide and serotonin-receptor agonists, also known as triptans, should be used together with caution. Serotonin syndrome has been reported during administration of serotonin-receptor agonists and non-selective monoamine oxidase inhibitors (MAOIs). Since safinamide selectively inhibits MAO-B at recommended doses, no interaction with serotonin-receptor agonists would be expected with normal prescription use. However, monitoring for serotonin-related side effects is advisable since the potential for serotonin syndrome exists. If serotonin syndrome occurs, discontinue all serotonergic agents and institute appropriate treatment.
Ephedrine: (Moderate) Severe hypertensive reactions, including hypertensive crisis, have been reported in patients taking monoamine oxidase inhibitors (MAOIs), such as safinamide, and sympathomimetic medications, such as ephedrine. If concomitant use of safinamide and ephedrine is necessary, monitor for hypertension and hypertensive crisis.
Ephedrine; Guaifenesin: (Moderate) Severe hypertensive reactions, including hypertensive crisis, have been reported in patients taking monoamine oxidase inhibitors (MAOIs), such as safinamide, and sympathomimetic medications, such as ephedrine. If concomitant use of safinamide and ephedrine is necessary, monitor for hypertension and hypertensive crisis.
Epinephrine: (Moderate) Severe hypertensive reactions, including hypertensive crisis, have been reported in patients taking monoamine oxidase inhibitors (MAOIs), such as safinamide, and sympathomimetic medications, such as epinephrine. If concomitant use of safinamide and epinephrine is necessary, monitor for hypertension and hypertensive crisis.
Escitalopram: (Major) The concurrent use of selective serotonin reuptake inhibitors (SSRIs) and monoamine oxidase inhibitors (MAOIs) is generally avoided; however, the manufacturer of safinamide recommends monitoring for serotonin syndrome and using the lowest effective dose of the SSRI during concurrent use. During clinical trial evaluation of safinamide, 1 case of serotonin syndrome occurred during co-administration with an SSRI. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death.
Esketamine: (Major) Because of the possibility of additive sedative effects, caution is advisable during concurrent use of dopaminergic agents, such as safinamide, and CNS depressants, such as esketamine. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. Patients who have received a dose of esketamine should be instructed not to drive or engage in other activities requiring complete mental alertness until the next day after a restful sleep.
Estazolam: (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of safinamide with other sedating medications, such as benzodiazepines.
Eszopiclone: (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of safinamide with other sedating medications, such as anxiolytics, sedatives, and hypnotics.
Ethanol: (Major) Advise patients to avoid alcohol consumption while taking safinamide. Alcohol consumption may increase the risk for somnolence and hypertension. Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Such events may increase when safinamide is combined with alcohol. Ingestion of alcohol-containing beverages with high tyramine content (i.e., more than 150 mg of tyramine) may also place some patients at risk for hypertension.
Fenfluramine: (Contraindicated) Coadministration of fenfluramine with safinamide or within 14 days after discontinuation of treatment with safinamide is contraindicated due to the risk of serotonin syndrome.
Fentanyl: (Contraindicated) Concomitant use of safinamide with opioids is contraindicated due to the risk of serotonin syndrome. Allow at least 14 days between discontinuation of safinamide and initiation of treatment with opioids.
Fexofenadine; Pseudoephedrine: (Moderate) Severe hypertensive reactions, including hypertensive crisis, have been reported in patients taking monoamine oxidase inhibitors (MAOIs), such as safinamide concurrently with sympathomimetic medications, such as pseudoephedrine. If concomitant use of safinamide and pseudoephedrine is necessary, monitor for hypertension and hypertensive crisis.
Fluoxetine: (Major) The concurrent use of selective serotonin reuptake inhibitors (SSRIs) and monoamine oxidase inhibitors (MAOIs) is generally avoided; however, the manufacturer of safinamide recommends monitoring for serotonin syndrome and using the lowest effective dose of the SSRI during concurrent use. During clinical trial evaluation of safinamide, 1 case of serotonin syndrome occurred during co-administration with an SSRI. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death.
Fluphenazine: (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and safinamide may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine if appropriate. If coadministration cannot be avoided, monitor for changes in movements, moods, or behaviors.
Flurazepam: (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of safinamide with other sedating medications, such as benzodiazepines.
Fluvoxamine: (Major) The concurrent use of selective serotonin reuptake inhibitors (SSRIs) and monoamine oxidase inhibitors (MAOIs) is generally avoided; however, the manufacturer of safinamide recommends monitoring for serotonin syndrome and using the lowest effective dose of the SSRI during concurrent use. During clinical trial evaluation of safinamide, 1 case of serotonin syndrome occurred during co-administration with an SSRI. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death.
Food: (Major) Advise patients to avoid cannabis use while taking CNS depressants due to the risk for additive CNS depression and potential for other cognitive adverse reactions. (Major) Safinamide is selective for MAO-B at recommended doses (50 to 100 mg/day) and can generally be used without dietary tyramine restriction. Patients should be informed not to exceed the recommended safinamide dose and to follow all dietary instructions. Certain foods may contain very high amounts (i.e., 150 mg or greater) of tyramine and could potentially cause a hypertensive reaction in individual patients with increased sensitivity to tyramine and are best avoided or limited. Food sources considered to be high in tyramine and that may interact with MAO inhibitors in general include Stilton aged cheese, concentrated yeast extracts (e.g., Marmite), aged meats, and sauerkraut. Ethanol ingestion of alcoholic beverages with high tyramine content (e.g., tap beers) also may place patients at risk. If a patient eats foods very rich in tyramine and does not feel well soon after eating, the patient should contact their healthcare provider. Patients should also be instructed to contact their healthcare provider if they experience severe headache, shortness of breath, palpitations, diaphoresis, chest pain or other symptoms suggestive of a significant hypertensive reaction or hypertensive crisis.
Frovatriptan: (Moderate) Safinamide and serotonin-receptor agonists, also known as triptans, should be used together with caution. Serotonin syndrome has been reported during administration of serotonin-receptor agonists and non-selective monoamine oxidase inhibitors (MAOIs). Since safinamide selectively inhibits MAO-B at recommended doses, no interaction with serotonin-receptor agonists would be expected with normal prescription use. However, monitoring for serotonin-related side effects is advisable since the potential for serotonin syndrome exists. If serotonin syndrome occurs, discontinue all serotonergic agents and institute appropriate treatment.
Gabapentin: (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and safinamide. Concomitant use of gabapentin with safinamide may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents, such as safinamide, have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Guaifenesin; Hydrocodone: (Contraindicated) Concomitant use of safinamide with opioids is contraindicated due to the risk of serotonin syndrome. Allow at least 14 days between discontinuation of safinamide and initiation of treatment with opioids.
Guaifenesin; Hydrocodone; Pseudoephedrine: (Contraindicated) Concomitant use of safinamide with opioids is contraindicated due to the risk of serotonin syndrome. Allow at least 14 days between discontinuation of safinamide and initiation of treatment with opioids. (Moderate) Severe hypertensive reactions, including hypertensive crisis, have been reported in patients taking monoamine oxidase inhibitors (MAOIs), such as safinamide concurrently with sympathomimetic medications, such as pseudoephedrine. If concomitant use of safinamide and pseudoephedrine is necessary, monitor for hypertension and hypertensive crisis.
Guaifenesin; Phenylephrine: (Moderate) Severe hypertensive reactions, including hypertensive crisis, have been reported in patients taking monoamine oxidase inhibitors (MAOIs), such as safinamide, and sympathomimetic medications, such as phenylephrine. If concomitant use of safinamide and phenylephrine is necessary, monitor for hypertension and hypertensive crisis.
Guaifenesin; Pseudoephedrine: (Moderate) Severe hypertensive reactions, including hypertensive crisis, have been reported in patients taking monoamine oxidase inhibitors (MAOIs), such as safinamide concurrently with sympathomimetic medications, such as pseudoephedrine. If concomitant use of safinamide and pseudoephedrine is necessary, monitor for hypertension and hypertensive crisis.
Haloperidol: (Major) Due to opposing effects on central dopaminergic activity, haloperidol and safinamide may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to haloperidol. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
Homatropine; Hydrocodone: (Contraindicated) Concomitant use of safinamide with opioids is contraindicated due to the risk of serotonin syndrome. Allow at least 14 days between discontinuation of safinamide and initiation of treatment with opioids.
Hydrocodone: (Contraindicated) Concomitant use of safinamide with opioids is contraindicated due to the risk of serotonin syndrome. Allow at least 14 days between discontinuation of safinamide and initiation of treatment with opioids.
Hydrocodone; Ibuprofen: (Contraindicated) Concomitant use of safinamide with opioids is contraindicated due to the risk of serotonin syndrome. Allow at least 14 days between discontinuation of safinamide and initiation of treatment with opioids.
Hydrocodone; Pseudoephedrine: (Contraindicated) Concomitant use of safinamide with opioids is contraindicated due to the risk of serotonin syndrome. Allow at least 14 days between discontinuation of safinamide and initiation of treatment with opioids. (Moderate) Severe hypertensive reactions, including hypertensive crisis, have been reported in patients taking monoamine oxidase inhibitors (MAOIs), such as safinamide concurrently with sympathomimetic medications, such as pseudoephedrine. If concomitant use of safinamide and pseudoephedrine is necessary, monitor for hypertension and hypertensive crisis.
Hydromorphone: (Contraindicated) Concomitant use of safinamide with opioids is contraindicated due to the risk of serotonin syndrome. Allow at least 14 days between discontinuation of safinamide and initiation of treatment with opioids.
Hydroxyzine: (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of other sedating medications, such as sedating H1-blockers.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Major) Concurrent use of intravenous (IV) methylene blue and MAOIs such as safinamide should generally be avoided due to the potential for serotonin syndrome. If emergent treatment with methylene blue is required in a patient receiving an MAOI it is advisable to discontinue the MAOI and monitor the patient for symptoms of CNS toxicity for two weeks or until 24 hours after the last dose of methylene blue, whichever comes first. During non-emergent use of methylene blue, it is advisable to discontinue the MAOI at least 2 weeks prior to methylene blue treatment, but also taking into consideration the half-life of the MAOI being discontinued. Because safinamide is a selective monoamine oxidase-B (MAO-B) inhibitor at manufacturer recommended doses, an interaction may be less likely to occur than with other traditional MAOIs. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A). Cases of serotonin syndrome have been reported, primarily following administration of IV methylene blue (1 to 8 mg/kg) as a visualizing agent in patients receiving serotonergic agents.
Ibuprofen; Oxycodone: (Contraindicated) Concomitant use of safinamide with opioids is contraindicated due to the risk of serotonin syndrome. Allow at least 14 days between discontinuation of safinamide and initiation of treatment with opioids.
Ibuprofen; Pseudoephedrine: (Moderate) Severe hypertensive reactions, including hypertensive crisis, have been reported in patients taking monoamine oxidase inhibitors (MAOIs), such as safinamide concurrently with sympathomimetic medications, such as pseudoephedrine. If concomitant use of safinamide and pseudoephedrine is necessary, monitor for hypertension and hypertensive crisis.
Iloperidone: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or safinamide during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and safinamide may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with safinamide than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
Imatinib: (Moderate) Safinamide at the 100 mg dose and its major metabolite may inhibit intestinal breast cancer resistance protein (BCRP), which could increase plasma concentrations of BCRP substrates such as imatinib. Monitor patients for increased pharmacologic or adverse effects of BCRP substrates during concurrent use of safinamide, particularly the 100 mg dose.
Imipramine: (Contraindicated) Safinamide is contraindicated for use with tricyclic antidepressants (TCAs) due to the risk of serotonin syndrome. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. At least 14 days should elapse between the discontinuation of safinamide and the initiation of a TCA.
Isocarboxazid: (Contraindicated) Concurrent use of safinamide with other monoamine oxidase inhibitors (MAOIs) or use of other MAOIs within 2 weeks of taking safinamide is contraindicated due to the risk of increased blood pressure, including hypertensive crisis. Serotonin syndrome has also been reported during coadministration of MAOIs, presumably due to additive effects on central serotonin levels.
Isoniazid, INH: (Major) Concurrent use of safinamide and isoniazid may increase the risk of a hypertensive crisis. Isoniazid has monoamine oxidase inhibiting activity and safinamide is a monoamine oxidase inhibitor (MAOI) type B. Monoamine oxidase type A is the primary enzyme in the gastrointestinal tract, and is responsible for the breakdown of dietary amines such as tyramine. When monoamine oxidase is inhibited by an MAOI, tyramine is absorbed systemically and may result in a hypertensive crisis. Although safinamide is a selective monoamine oxidase inhibitor type B, there is a risk of hypertension during ingestion of substances high in tyramine or during concurrent use of other drugs with MAOI activity such as isoniazid, since the MAOI-B selectivity of safinamide decreases with increasing dosages.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Concurrent use of safinamide and isoniazid may increase the risk of a hypertensive crisis. Isoniazid has monoamine oxidase inhibiting activity and safinamide is a monoamine oxidase inhibitor (MAOI) type B. Monoamine oxidase type A is the primary enzyme in the gastrointestinal tract, and is responsible for the breakdown of dietary amines such as tyramine. When monoamine oxidase is inhibited by an MAOI, tyramine is absorbed systemically and may result in a hypertensive crisis. Although safinamide is a selective monoamine oxidase inhibitor type B, there is a risk of hypertension during ingestion of substances high in tyramine or during concurrent use of other drugs with MAOI activity such as isoniazid, since the MAOI-B selectivity of safinamide decreases with increasing dosages.
Isoniazid, INH; Rifampin: (Major) Concurrent use of safinamide and isoniazid may increase the risk of a hypertensive crisis. Isoniazid has monoamine oxidase inhibiting activity and safinamide is a monoamine oxidase inhibitor (MAOI) type B. Monoamine oxidase type A is the primary enzyme in the gastrointestinal tract, and is responsible for the breakdown of dietary amines such as tyramine. When monoamine oxidase is inhibited by an MAOI, tyramine is absorbed systemically and may result in a hypertensive crisis. Although safinamide is a selective monoamine oxidase inhibitor type B, there is a risk of hypertension during ingestion of substances high in tyramine or during concurrent use of other drugs with MAOI activity such as isoniazid, since the MAOI-B selectivity of safinamide decreases with increasing dosages.
Isoproterenol: (Moderate) Severe hypertensive reactions, including hypertensive crisis, have been reported in patients taking monoamine oxidase inhibitors (MAOIs), such as safinamide, and sympathomimetic medications, such as isoproterenol. If concomitant use of safinamide and isoproterenol is necessary, monitor for hypertension and hypertensive crisis.
Lasmiditan: (Moderate) Monitor for excessive sedation, somnolence, and serotonin syndrome during coadministration of lasmiditan and safinamide. Inform patients taking this combination of the risks and symptoms of excessive CNS depression and serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Dopaminergic agents, such as safinamide, have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Lemborexant: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and safinamide. Dosage adjustments of lemborexant and safinamide may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Levocetirizine: (Moderate) Concurrent use of cetirizine/levocetirizine with safinamide should generally be avoided because of the possibility of additive sedative effects. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Levodopa: (Moderate) Safinamide and carbidopa; levodopa are indicated for use in combination; however, there is the possibility of new onset dyskinesias or exacerbation of pre-existing dyskinesias. Patients should be advised to contact their health care provider if they notice new or worsening dyskinesias while taking these medicines together.
Levomilnacipran: (Contraindicated) Safinamide is contraindicated for use with serotonin norepinephrine reuptake inhibitors (SNRIs) due to the risk of serotonin syndrome. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. At least 14 days should elapse between the discontinuation of safinamide and the initiation of an SNRI.
Levorphanol: (Contraindicated) Concomitant use of safinamide with opioids is contraindicated due to the risk of serotonin syndrome. Allow at least 14 days between discontinuation of safinamide and initiation of treatment with opioids.
Lidocaine; Epinephrine: (Moderate) Severe hypertensive reactions, including hypertensive crisis, have been reported in patients taking monoamine oxidase inhibitors (MAOIs), such as safinamide, and sympathomimetic medications, such as epinephrine. If concomitant use of safinamide and epinephrine is necessary, monitor for hypertension and hypertensive crisis.
Linezolid: (Contraindicated) Concurrent use of linezolid with safinamide, a monoamine oxidase inhibitor type B, or use of linezolid within 2 weeks of taking safinamide is contraindicated due to the risk of increased blood pressure, including hypertensive crisis. Linezolid is an antibiotic that is also a potent inhibitor of monoamine oxidase. Serotonin syndrome has also been reported when linezolid is given with serotonergic agents, including monoamine oxidase inhibitors (MAOIs), which can potentiate central serotonin levels.
Lisdexamfetamine: (Contraindicated) Safinamide, a selective monoamine oxidase-B inhibitor, is contraindicated for use with amphetamines due to the risk of serotonin syndrome or hypertensive crisis. The manufacturer of safinamide recommends that a period of at least 14 days elapse between the discontinuation of safinamide and the initiation of serotonergic agents. Hypertensive crisis has been reported in patients taking recommended doses of selective MAO-B inhibitors and sympathomimetic medications, such as amphetamines. Safinamide can cause hypertension or exacerbate existing hypertension, particularly at daily dosages exceeding those recommended by the manufacturer.
Loratadine; Pseudoephedrine: (Moderate) Severe hypertensive reactions, including hypertensive crisis, have been reported in patients taking monoamine oxidase inhibitors (MAOIs), such as safinamide concurrently with sympathomimetic medications, such as pseudoephedrine. If concomitant use of safinamide and pseudoephedrine is necessary, monitor for hypertension and hypertensive crisis.
Lorazepam: (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of safinamide with other sedating medications, such as benzodiazepines.
Loxapine: (Major) Due to opposing effects on central dopaminergic activity, loxapine and safinamide may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to loxapine. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
Lumateperone: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or safinamide during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and safinamide may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with safinamide than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
Lurasidone: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or safinamide during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and safinamide may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with safinamide than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
Maprotiline: (Contraindicated) According to the manufacturer of safinamide, the concurrent use of safinamide and heterocyclic antidepressants, such as maprotiline, is contraindicated due to the risk of serotonin syndrome. At least 14 days should elapse between the discontinuation of safinamide and the initiation of maprotiline.
Meclizine: (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of other sedating medications, such as sedating H1-blockers.
Meperidine: (Contraindicated) Concomitant use of safinamide with opioids is contraindicated due to the risk of serotonin syndrome. Allow at least 14 days between discontinuation of safinamide and initiation of treatment with opioids.
Meperidine; Promethazine: (Contraindicated) Concomitant use of safinamide with opioids is contraindicated due to the risk of serotonin syndrome. Allow at least 14 days between discontinuation of safinamide and initiation of treatment with opioids. (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and safinamide may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine if appropriate. If coadministration cannot be avoided, monitor for changes in movements, moods, or behaviors.
Meprobamate: (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of safinamide with other sedating medications, such as anxiolytics, sedatives, and hypnotics.
Methadone: (Contraindicated) Concomitant use of safinamide with opioids is contraindicated due to the risk of serotonin syndrome. Allow at least 14 days between discontinuation of safinamide and initiation of treatment with opioids.
Methamphetamine: (Contraindicated) Safinamide, a selective monoamine oxidase-B inhibitor, is contraindicated for use with amphetamines due to the risk of serotonin syndrome or hypertensive crisis. The manufacturer of safinamide recommends that a period of at least 14 days elapse between the discontinuation of safinamide and the initiation of serotonergic agents. Hypertensive crisis has been reported in patients taking recommended doses of selective MAO-B inhibitors and sympathomimetic medications, such as amphetamines. Safinamide can cause hypertension or exacerbate existing hypertension, particularly at daily dosages exceeding those recommended by the manufacturer.
Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Major) Concurrent use of intravenous (IV) methylene blue and MAOIs such as safinamide should generally be avoided due to the potential for serotonin syndrome. If emergent treatment with methylene blue is required in a patient receiving an MAOI it is advisable to discontinue the MAOI and monitor the patient for symptoms of CNS toxicity for two weeks or until 24 hours after the last dose of methylene blue, whichever comes first. During non-emergent use of methylene blue, it is advisable to discontinue the MAOI at least 2 weeks prior to methylene blue treatment, but also taking into consideration the half-life of the MAOI being discontinued. Because safinamide is a selective monoamine oxidase-B (MAO-B) inhibitor at manufacturer recommended doses, an interaction may be less likely to occur than with other traditional MAOIs. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A). Cases of serotonin syndrome have been reported, primarily following administration of IV methylene blue (1 to 8 mg/kg) as a visualizing agent in patients receiving serotonergic agents.
Methohexital: (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of safinamide with other sedating medications, such as barbiturates.
Methotrexate: (Moderate) Safinamide at the 100 mg dose and its major metabolite may inhibit intestinal breast cancer resistance protein (BCRP), which could increase plasma concentrations of BCRP substrates such as methotrexate. Monitor patients for increased pharmacologic or adverse effects of BCRP substrates during concurrent use of safinamide, particularly the 100 mg dose.
Methylene Blue: (Major) Concurrent use of intravenous (IV) methylene blue and MAOIs such as safinamide should generally be avoided due to the potential for serotonin syndrome. If emergent treatment with methylene blue is required in a patient receiving an MAOI it is advisable to discontinue the MAOI and monitor the patient for symptoms of CNS toxicity for two weeks or until 24 hours after the last dose of methylene blue, whichever comes first. During non-emergent use of methylene blue, it is advisable to discontinue the MAOI at least 2 weeks prior to methylene blue treatment, but also taking into consideration the half-life of the MAOI being discontinued. Because safinamide is a selective monoamine oxidase-B (MAO-B) inhibitor at manufacturer recommended doses, an interaction may be less likely to occur than with other traditional MAOIs. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A). Cases of serotonin syndrome have been reported, primarily following administration of IV methylene blue (1 to 8 mg/kg) as a visualizing agent in patients receiving serotonergic agents.
Methylphenidate Derivatives: (Contraindicated) Safinamide, a selective monoamine oxidase-B inhibitor, is contraindicated for use with methylphenidate and its derivatives due to the risk of serotonin syndrome and hypertensive crisis. The manufacturer of safinamide recommends that a period of at least 14 days elapse between the discontinuation of safinamide and the initiation of serotonergic agents. Hypertensive crisis has been reported in patients taking recommended doses of selective MAO-B inhibitors and sympathomimetic medications, such as methylphenidate. Safinamide can cause hypertension or exacerbate existing hypertension, particularly at daily dosages exceeding those recommended by the manufacturer.
Metoclopramide: (Major) The concurrent use of safinamide and metoclopramide should be avoided if possible. The beneficial effects of safinamide are mediated by monoamine oxidase inhibitor type B activity which increases central dopamine availability and metoclopramide is a dopamine antagonist. In addition, metoclopramide may cause extrapyramidal effects, including pseudoparkinsonism. If these agents must be used together, monitor for exacerbation of Parkinson's disease symptoms.
Midazolam: (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of safinamide with other sedating medications, such as benzodiazepines.
Midodrine: (Moderate) Severe hypertensive reactions, including hypertensive crisis, have been reported in patients taking monoamine oxidase inhibitors (MAOIs), such as safinamide, and sympathomimetic medications, such as midodrine. If concomitant use of safinamide and midodrine is necessary, monitor for hypertension and hypertensive crisis.
Milnacipran: (Contraindicated) Safinamide is contraindicated for use with serotonin norepinephrine reuptake inhibitors (SNRIs) due to the risk of serotonin syndrome. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. At least 14 days should elapse between the discontinuation of safinamide and the initiation of an SNRI.
Mitoxantrone: (Moderate) Safinamide at the 100 mg dose and its major metabolite may inhibit intestinal breast cancer resistance protein (BCRP), which could increase plasma concentrations of BCRP substrates such as mitoxantrone. Monitor patients for increased pharmacologic or adverse effects of BCRP substrates during concurrent use of safinamide, particularly the 100 mg dose.
Molindone: (Major) Due to opposing effects on central dopaminergic activity, safinamide and molindone may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to molindone. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
Monoamine oxidase inhibitors: (Contraindicated) Concurrent use of safinamide with other monoamine oxidase inhibitors (MAOIs) or use of other MAOIs within 2 weeks of taking safinamide is contraindicated due to the risk of increased blood pressure, including hypertensive crisis. Serotonin syndrome has also been reported during coadministration of MAOIs, presumably due to additive effects on central serotonin levels.
Morphine: (Contraindicated) Concomitant use of safinamide with opioids is contraindicated due to the risk of serotonin syndrome. Allow at least 14 days between discontinuation of safinamide and initiation of treatment with opioids.
Morphine; Naltrexone: (Contraindicated) Concomitant use of safinamide with opioids is contraindicated due to the risk of serotonin syndrome. Allow at least 14 days between discontinuation of safinamide and initiation of treatment with opioids.
Nabilone: (Major) Because of the possibility of additive sedative effects, caution is advisable during concurrent use of dopaminergic agents, such as safinamide, and CNS depressants. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Nalbuphine: (Contraindicated) Concomitant use of safinamide with opioids is contraindicated due to the risk of serotonin syndrome. Allow at least 14 days between discontinuation of safinamide and initiation of treatment with opioids.
Naproxen; Pseudoephedrine: (Moderate) Severe hypertensive reactions, including hypertensive crisis, have been reported in patients taking monoamine oxidase inhibitors (MAOIs), such as safinamide concurrently with sympathomimetic medications, such as pseudoephedrine. If concomitant use of safinamide and pseudoephedrine is necessary, monitor for hypertension and hypertensive crisis.
Naratriptan: (Moderate) Safinamide and serotonin-receptor agonists, also known as triptans, should be used together with caution. Serotonin syndrome has been reported during administration of serotonin-receptor agonists and non-selective monoamine oxidase inhibitors (MAOIs). Since safinamide selectively inhibits MAO-B at recommended doses, no interaction with serotonin-receptor agonists would be expected with normal prescription use. However, monitoring for serotonin-related side effects is advisable since the potential for serotonin syndrome exists. If serotonin syndrome occurs, discontinue all serotonergic agents and institute appropriate treatment.
Norepinephrine: (Moderate) Severe hypertensive reactions, including hypertensive crisis, have been reported in patients taking monoamine oxidase inhibitors (MAOIs), such as safinamide, and sympathomimetic medications, such as norepinephrine. If concomitant use of safinamide and norepinephrine is necessary, monitor for hypertension and hypertensive crisis.
Nortriptyline: (Contraindicated) Safinamide is contraindicated for use with tricyclic antidepressants (TCAs) due to the risk of serotonin syndrome. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. At least 14 days should elapse between the discontinuation of safinamide and the initiation of a TCA.
Olanzapine: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or safinamide during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and safinamide may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with safinamide than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
Olanzapine; Fluoxetine: (Major) The concurrent use of selective serotonin reuptake inhibitors (SSRIs) and monoamine oxidase inhibitors (MAOIs) is generally avoided; however, the manufacturer of safinamide recommends monitoring for serotonin syndrome and using the lowest effective dose of the SSRI during concurrent use. During clinical trial evaluation of safinamide, 1 case of serotonin syndrome occurred during co-administration with an SSRI. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or safinamide during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and safinamide may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with safinamide than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
Olanzapine; Samidorphan: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or safinamide during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and safinamide may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with safinamide than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
Oliceridine: (Contraindicated) Concomitant use of safinamide with opioids is contraindicated due to the risk of serotonin syndrome. Allow at least 14 days between discontinuation of safinamide and initiation of treatment with opioids.
Opiate Agonists: (Contraindicated) Concomitant use of safinamide with opioids is contraindicated due to the risk of serotonin syndrome. Allow at least 14 days between discontinuation of safinamide and initiation of treatment with opioids.
Opiate Agonists-Antagonists: (Contraindicated) Concomitant use of safinamide with opioids is contraindicated due to the risk of serotonin syndrome. Allow at least 14 days between discontinuation of safinamide and initiation of treatment with opioids.
Oxazepam: (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of safinamide with other sedating medications, such as benzodiazepines.
Oxycodone: (Contraindicated) Concomitant use of safinamide with opioids is contraindicated due to the risk of serotonin syndrome. Allow at least 14 days between discontinuation of safinamide and initiation of treatment with opioids.
Oxymorphone: (Contraindicated) Concomitant use of safinamide with opioids is contraindicated due to the risk of serotonin syndrome. Allow at least 14 days between discontinuation of safinamide and initiation of treatment with opioids.
Ozanimod: (Contraindicated) Coadministration of ozanimod with monoamine oxidase (MAO) inhibitors, like safinamide, is contraindicated. Allow at least 14 days between discontinuation of ozanimod and initiation of treatment with safinamide. Metabolites of ozanimod may inhibit MAO. The potential for a clinical interaction with MAO inhibitors has not been studied; however, the increased risk of nonselective MAO inhibition may lead to a hypertensive crisis. In addition, MAOB inhibitors, such as safinamide, may decrease exposure of the active metabolites of ozanimod.
Paliperidone: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or safinamide during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and safinamide may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with safinamide than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
Paroxetine: (Major) The concurrent use of selective serotonin reuptake inhibitors (SSRIs) and monoamine oxidase inhibitors (MAOIs) is generally avoided; however, the manufacturer of safinamide recommends monitoring for serotonin syndrome and using the lowest effective dose of the SSRI during concurrent use. During clinical trial evaluation of safinamide, 1 case of serotonin syndrome occurred during co-administration with an SSRI. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death.
Pentazocine: (Contraindicated) Concomitant use of safinamide with opioids is contraindicated due to the risk of serotonin syndrome. Allow at least 14 days between discontinuation of safinamide and initiation of treatment with opioids.
Pentazocine; Naloxone: (Contraindicated) Concomitant use of safinamide with opioids is contraindicated due to the risk of serotonin syndrome. Allow at least 14 days between discontinuation of safinamide and initiation of treatment with opioids.
Pentobarbital: (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of safinamide with other sedating medications, such as barbiturates.
Perphenazine: (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and safinamide may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine if appropriate. If coadministration cannot be avoided, monitor for changes in movements, moods, or behaviors.
Perphenazine; Amitriptyline: (Contraindicated) Safinamide is contraindicated for use with tricyclic antidepressants (TCAs) due to the risk of serotonin syndrome. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. At least 14 days should elapse between the discontinuation of safinamide and the initiation of a TCA. (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and safinamide may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine if appropriate. If coadministration cannot be avoided, monitor for changes in movements, moods, or behaviors.
Phendimetrazine: (Moderate) Severe hypertensive reactions, including hypertensive crisis, have been reported in patients taking monoamine oxidase inhibitors (MAOIs), such as safinamide, and sympathomimetic medications, such as phendimetrazine. If concomitant use of safinamide and phendimetrazine is necessary, monitor for hypertension and hypertensive crisis.
Phenelzine: (Contraindicated) Concurrent use of safinamide with other monoamine oxidase inhibitors (MAOIs) or use of other MAOIs within 2 weeks of taking safinamide is contraindicated due to the risk of increased blood pressure, including hypertensive crisis. Serotonin syndrome has also been reported during coadministration of MAOIs, presumably due to additive effects on central serotonin levels.
Phenobarbital: (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of safinamide with other sedating medications, such as barbiturates.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of safinamide with other sedating medications, such as barbiturates.
Phenothiazines: (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and safinamide may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine if appropriate. If coadministration cannot be avoided, monitor for changes in movements, moods, or behaviors.
Phentermine: (Moderate) Severe hypertensive reactions, including hypertensive crisis, have been reported in patients taking monoamine oxidase inhibitors (MAOIs), such as safinamide, and sympathomimetic medications, such as phentermine. If concomitant use of safinamide and phentermine is necessary, monitor for hypertension and hypertensive crisis.
Phentermine; Topiramate: (Moderate) Severe hypertensive reactions, including hypertensive crisis, have been reported in patients taking monoamine oxidase inhibitors (MAOIs), such as safinamide, and sympathomimetic medications, such as phentermine. If concomitant use of safinamide and phentermine is necessary, monitor for hypertension and hypertensive crisis.
Phenylephrine: (Moderate) Severe hypertensive reactions, including hypertensive crisis, have been reported in patients taking monoamine oxidase inhibitors (MAOIs), such as safinamide, and sympathomimetic medications, such as phenylephrine. If concomitant use of safinamide and phenylephrine is necessary, monitor for hypertension and hypertensive crisis.
Pimozide: (Major) Due to opposing effects on central dopaminergic activity, pimozide and safinamide may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to pimozide. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
Pregabalin: (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and safinamide. Concomitant use of pregabalin with safinamide may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents, such as safinamide, have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Prilocaine; Epinephrine: (Moderate) Severe hypertensive reactions, including hypertensive crisis, have been reported in patients taking monoamine oxidase inhibitors (MAOIs), such as safinamide, and sympathomimetic medications, such as epinephrine. If concomitant use of safinamide and epinephrine is necessary, monitor for hypertension and hypertensive crisis.
Primidone: (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of safinamide with other sedating medications, such as barbiturates.
Prochlorperazine: (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and safinamide may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine if appropriate. If coadministration cannot be avoided, monitor for changes in movements, moods, or behaviors.
Promethazine: (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and safinamide may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine if appropriate. If coadministration cannot be avoided, monitor for changes in movements, moods, or behaviors.
Promethazine; Dextromethorphan: (Contraindicated) Dextromethorphan prescription products are contraindicated in patients taking monoamine oxidase inhibitors (MAOIs) or in patients who have taken MAOIs within the preceding 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. Allow at least 14 days after stopping dextromethorphan before starting an MAOI, including safinamide. Brief episodes of psychosis or bizarre behavior have also been reported with this combination. Patients should read nonprescription product labels carefully. Before initiating an MAOI after using other serotoninergic agents, a sufficient amount of time must be allowed for clearance of the serotoninergic agent and its active metabolites. (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and safinamide may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine if appropriate. If coadministration cannot be avoided, monitor for changes in movements, moods, or behaviors.
Promethazine; Phenylephrine: (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and safinamide may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine if appropriate. If coadministration cannot be avoided, monitor for changes in movements, moods, or behaviors. (Moderate) Severe hypertensive reactions, including hypertensive crisis, have been reported in patients taking monoamine oxidase inhibitors (MAOIs), such as safinamide, and sympathomimetic medications, such as phenylephrine. If concomitant use of safinamide and phenylephrine is necessary, monitor for hypertension and hypertensive crisis.
Protriptyline: (Contraindicated) Safinamide is contraindicated for use with tricyclic antidepressants (TCAs) due to the risk of serotonin syndrome. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. At least 14 days should elapse between the discontinuation of safinamide and the initiation of a TCA.
Pseudoephedrine: (Moderate) Severe hypertensive reactions, including hypertensive crisis, have been reported in patients taking monoamine oxidase inhibitors (MAOIs), such as safinamide concurrently with sympathomimetic medications, such as pseudoephedrine. If concomitant use of safinamide and pseudoephedrine is necessary, monitor for hypertension and hypertensive crisis.
Pseudoephedrine; Triprolidine: (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of other sedating medications, such as sedating H1-blockers. (Moderate) Severe hypertensive reactions, including hypertensive crisis, have been reported in patients taking monoamine oxidase inhibitors (MAOIs), such as safinamide concurrently with sympathomimetic medications, such as pseudoephedrine. If concomitant use of safinamide and pseudoephedrine is necessary, monitor for hypertension and hypertensive crisis.
Pyrilamine: (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of other sedating medications, such as sedating H1-blockers.
Quazepam: (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of safinamide with other sedating medications, such as benzodiazepines.
Quetiapine: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or safinamide during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and safinamide may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with safinamide than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
Racepinephrine: (Moderate) Severe hypertensive reactions, including hypertensive crisis, have been reported in patients taking monoamine oxidase inhibitors (MAOIs), such as safinamide, and sympathomimetic medications, such as racepinephrine. If concomitant use of safinamide and racepinephrine is necessary, monitor for hypertension and hypertensive crisis.
Ramelteon: (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of safinamide with other sedating medications, such as Ramelteon.
Rasagiline: (Contraindicated) Concurrent use of Safinamide with medications that inhibit monoamine oxidase B, such as rasagiline, or use of rasagiline within 2 weeks of taking safinamide is contraindicated due to the risk of increased blood pressure, including hypertensive crisis. Serotonin syndrome has also been reported during co-administration of monoamine oxidase inhibitors (MAOIs), which can potentiate central serotonin levels.
Remifentanil: (Contraindicated) Concomitant use of safinamide with opioids is contraindicated due to the risk of serotonin syndrome. Allow at least 14 days between discontinuation of safinamide and initiation of treatment with opioids.
Remimazolam: (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of safinamide with other sedating medications, such as benzodiazepines.
Risperidone: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or safinamide during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and safinamide may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with safinamide than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
Rizatriptan: (Moderate) Safinamide and serotonin-receptor agonists, also known as triptans, should be used together with caution. Serotonin syndrome has been reported during administration of serotonin-receptor agonists and non-selective monoamine oxidase inhibitors (MAOIs). Since safinamide selectively inhibits MAO-B at recommended doses, no interaction with serotonin-receptor agonists would be expected with normal prescription use. However, monitoring for serotonin-related side effects is advisable since the potential for serotonin syndrome exists. If serotonin syndrome occurs, discontinue all serotonergic agents and institute appropriate treatment.
Rosuvastatin: (Moderate) Safinamide at the 100 mg dose and its major metabolite may inhibit intestinal breast cancer resistance protein (BCRP), which could increase plasma concentrations of BCRP substrates such as rosuvastatin. Monitor patients for increased pharmacologic or adverse effects of BCRP substrates during concurrent use of safinamide, particularly the 100 mg dose.
Rosuvastatin; Ezetimibe: (Moderate) Safinamide at the 100 mg dose and its major metabolite may inhibit intestinal breast cancer resistance protein (BCRP), which could increase plasma concentrations of BCRP substrates such as rosuvastatin. Monitor patients for increased pharmacologic or adverse effects of BCRP substrates during concurrent use of safinamide, particularly the 100 mg dose.
Secobarbital: (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of safinamide with other sedating medications, such as barbiturates.
Sedating H1-blockers: (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of other sedating medications, such as sedating H1-blockers.
Selective serotonin reuptake inhibitors: (Major) The concurrent use of selective serotonin reuptake inhibitors (SSRIs) and monoamine oxidase inhibitors (MAOIs) is generally avoided; however, the manufacturer of safinamide recommends monitoring for serotonin syndrome and using the lowest effective dose of the SSRI during concurrent use. During clinical trial evaluation of safinamide, 1 case of serotonin syndrome occurred during co-administration with an SSRI. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death.
Selegiline: (Contraindicated) Both safinamide and selegiline are selective monoamine oxidase type B inhibitors (MAO-B inhibitors), and concurrent use is contraindicated. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with safinamide. After stopping treatment with safinamide, a time period equal to 4 to 5 half-lives of safinamide or any active metabolite should elapse before starting therapy with selegiline. Hypertensive crisis has occurred in patients receiving selective MAO-B inhibitors simultaneously. Concurrent use may also represent duplicative therapy.
Serotonin norepinephrine reuptake inhibitors: (Contraindicated) Safinamide is contraindicated for use with serotonin norepinephrine reuptake inhibitors (SNRIs) due to the risk of serotonin syndrome. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. At least 14 days should elapse between the discontinuation of safinamide and the initiation of an SNRI.
Serotonin-Receptor Agonists: (Moderate) Safinamide and serotonin-receptor agonists, also known as triptans, should be used together with caution. Serotonin syndrome has been reported during administration of serotonin-receptor agonists and non-selective monoamine oxidase inhibitors (MAOIs). Since safinamide selectively inhibits MAO-B at recommended doses, no interaction with serotonin-receptor agonists would be expected with normal prescription use. However, monitoring for serotonin-related side effects is advisable since the potential for serotonin syndrome exists. If serotonin syndrome occurs, discontinue all serotonergic agents and institute appropriate treatment.
Sertraline: (Major) The concurrent use of selective serotonin reuptake inhibitors (SSRIs) and monoamine oxidase inhibitors (MAOIs) is generally avoided; however, the manufacturer of safinamide recommends monitoring for serotonin syndrome and using the lowest effective dose of the SSRI during concurrent use. During clinical trial evaluation of safinamide, 1 case of serotonin syndrome occurred during co-administration with an SSRI. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death.
Solriamfetol: (Contraindicated) The concurrent use of solriamfetol, a noradrenergic drugs, and safinamide, a monoamine oxidase inhibitor, or use of solriamfetol within 14 days of safinamide is contraindicated due to the increased risk for hypertensive crisis. Potential outcomes include death, stroke, myocardial infarction, aortic dissection, ophthalmological complications, eclampsia, pulmonary edema, and renal failure. In addition, solriamfetol is a central dopaminergic drug and concurrent use with other dopaminergic drugs, such as safinamide, has not been studied.
St. John's Wort, Hypericum perforatum: (Contraindicated) Safinamide is contraindicated for use with St. John's Wort due to the risk of serotonin syndrome. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. At least 14 days should elapse between the discontinuation of safinamide and the initiation of St. John's Wort. Patients should be instructed to discuss the use of any vitamins or herbal supplements with their heatlh care provider prior to the initiation of any new medication.
Stiripentol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and safinamide. CNS depressants can potentiate the effects of stiripentol.
Sufentanil: (Contraindicated) Concomitant use of safinamide with opioids is contraindicated due to the risk of serotonin syndrome. Allow at least 14 days between discontinuation of safinamide and initiation of treatment with opioids.
Sulfasalazine: (Moderate) Safinamide at the 100 mg dose and its major metabolite may inhibit intestinal breast cancer resistance protein (BCRP), which could increase plasma concentrations of BCRP substrates such as sulfasalazine. Monitor patients for increased pharmacologic or adverse effects of BCRP substrates during concurrent use of safinamide, particularly the 100 mg dose.
Sumatriptan: (Moderate) Safinamide and serotonin-receptor agonists, also known as triptans, should be used together with caution. Serotonin syndrome has been reported during administration of serotonin-receptor agonists and non-selective monoamine oxidase inhibitors (MAOIs). Since safinamide selectively inhibits MAO-B at recommended doses, no interaction with serotonin-receptor agonists would be expected with normal prescription use. However, monitoring for serotonin-related side effects is advisable since the potential for serotonin syndrome exists. If serotonin syndrome occurs, discontinue all serotonergic agents and institute appropriate treatment.
Sumatriptan; Naproxen: (Moderate) Safinamide and serotonin-receptor agonists, also known as triptans, should be used together with caution. Serotonin syndrome has been reported during administration of serotonin-receptor agonists and non-selective monoamine oxidase inhibitors (MAOIs). Since safinamide selectively inhibits MAO-B at recommended doses, no interaction with serotonin-receptor agonists would be expected with normal prescription use. However, monitoring for serotonin-related side effects is advisable since the potential for serotonin syndrome exists. If serotonin syndrome occurs, discontinue all serotonergic agents and institute appropriate treatment.
Suvorexant: (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of safinamide with other sedating medications, such as suvorexant.
Talazoparib: (Major) Avoid coadministration of safinamide with talazoparib due to increased talazoparib exposure. If concomitant use is unavoidable, monitor for an increase in talazoparib-related adverse reactions. Talazoparib is a BCRP substrate and safinamide is a BCRP inhibitor. The effect of concomitant administration of BCRP inhibitors on the pharmacokinetics of talazoparib has not been studied; however, BCRP inhibitors may increase talazoparib exposure.
Tapentadol: (Contraindicated) Concomitant use of safinamide with opioids is contraindicated due to the risk of serotonin syndrome. Allow at least 14 days between discontinuation of safinamide and initiation of treatment with opioids.
Tasimelteon: (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of safinamide with other sedating medications, such as tasimelteon.
Temazepam: (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of safinamide with other sedating medications, such as benzodiazepines.
Tetrabenazine: (Contraindicated) Tetrabenazine use is contraindicated in patients who are receiving or have received a monoamine oxidase inhibitor, such as safinamide, within the past 14 days. The major metabolites of tetrabenazine (alpha-dihydrotetrabenazine [HTBZ] and beta-HTBZ) are reversible inhibitors of vesicular monoamine transporter 2 (VMAT2). Inhibition of VMAT2 results in decreased uptake of monoamines into synaptic vesicles and depletion of monoamine stores.
Thiethylperazine: (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and safinamide may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine if appropriate. If coadministration cannot be avoided, monitor for changes in movements, moods, or behaviors.
Thioridazine: (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and safinamide may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine if appropriate. If coadministration cannot be avoided, monitor for changes in movements, moods, or behaviors.
Thiothixene: (Major) Due to opposing effects on central dopaminergic activity, thiothixene and safinamide may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to thiothixene. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
Topotecan: (Major) Avoid coadministration of safinamide with oral topotecan due to increased topotecan exposure; safinamide may be administered with intravenous topotecan. Oral topotecan is a substrate of the Breast Cancer Resistance Protein (BCRP) and safinamide is a BCRP inhibitor. Coadministration increases the risk of topotecan-related adverse reactions.
Tramadol: (Contraindicated) Concomitant use of safinamide with opioids is contraindicated due to the risk of serotonin syndrome. Allow at least 14 days between discontinuation of safinamide and initiation of treatment with opioids.
Tramadol; Acetaminophen: (Contraindicated) Concomitant use of safinamide with opioids is contraindicated due to the risk of serotonin syndrome. Allow at least 14 days between discontinuation of safinamide and initiation of treatment with opioids.
Tranylcypromine: (Contraindicated) Concurrent use of safinamide with other monoamine oxidase inhibitors (MAOIs) or use of other MAOIs within 2 weeks of taking safinamide is contraindicated due to the risk of increased blood pressure, including hypertensive crisis. Serotonin syndrome has also been reported during coadministration of MAOIs, presumably due to additive effects on central serotonin levels.
Trazodone: (Contraindicated) Safinamide is contraindicated for use with trazodone due to the risk of serotonin syndrome. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. At least 14 days should elapse between the discontinuation of safinamide and the initiation of trazodone.
Triazolam: (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of safinamide with other sedating medications, such as benzodiazepines.
Tricyclic antidepressants: (Contraindicated) Safinamide is contraindicated for use with tricyclic antidepressants (TCAs) due to the risk of serotonin syndrome. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. At least 14 days should elapse between the discontinuation of safinamide and the initiation of a TCA.
Trifluoperazine: (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and safinamide may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine if appropriate. If coadministration cannot be avoided, monitor for changes in movements, moods, or behaviors.
Trimipramine: (Contraindicated) Safinamide is contraindicated for use with tricyclic antidepressants (TCAs) due to the risk of serotonin syndrome. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. At least 14 days should elapse between the discontinuation of safinamide and the initiation of a TCA.
Triprolidine: (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of other sedating medications, such as sedating H1-blockers.
Tryptophan, 5-Hydroxytryptophan: (Major) Avoid use together if possible. The combination of tryptophan supplements and safinamide may lead to increased levels of serotonin and serotonin syndrome. Tryptophan is a serotonin precursor. Safinamide is a MAO-B inhibitor. In the postmarketing period, potentially life-threatening serotonin syndrome has been reported in patients treated with selected serotonergic agents concomitantly with selective MAO-B inhibitors. There are also reports of tryptophan and MAO inhibitor interactions in the literature.
Ubrogepant: (Major) Limit the initial and second dose of ubrogepant to 50 mg if coadministered with safinamide. Concurrent use may increase ubrogepant exposure and the risk of adverse effects. Ubrogepant is a substrate of the BCRP and P-gp drug transporters; safinamide is a BCRP and P-gp inhibitor.
Valbenazine: (Major) Avoid the use of valbenazine with safinamide if possible. Safinamide is a selective inhibitor of MAO type B (MAO-B), which results in an increased bioavailability of dopamine in the brain, while the therapeutic effect of valbenazine is thought to occur through inhibition of dopamine release. Concomitant use of valbenazine and safinamide may result in an attenuated treatment effect of valbenazine or safinamide.
Venlafaxine: (Contraindicated) Safinamide is contraindicated for use with serotonin norepinephrine reuptake inhibitors (SNRIs) due to the risk of serotonin syndrome. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. At least 14 days should elapse between the discontinuation of safinamide and the initiation of an SNRI.
Vilazodone: (Contraindicated) Concurrent use of vilazodone and safinamide, a monoamine oxidase inhibitor (MAOI), or use of vilazodone within 2 weeks of stopping safinamide is contraindicated due to the risk of serotonin syndrome. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death.
Viloxazine: (Contraindicated) Concurrent use of viloxazine with safinamide or within two weeks after discontinuing safinamide is contraindicated due to the risk for hypertensive crisis.
Vortioxetine: (Contraindicated) Concurrent use of vortioxetine and safinamide, a monoamine oxidase inhibitor (MAOI), or use of safinamide within 2 weeks of stopping vortioxetine is contraindicated due to the risk of serotonin syndrome. Conversely, at least 21 days should elapse after stopping vortioxetine before initiating safinamide. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death.
Zaleplon: (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of safinamide with other sedating medications, such as anxiolytics, sedatives, and hypnotics.
Ziprasidone: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or safinamide during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and safinamide may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with safinamide than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
Zolmitriptan: (Moderate) Safinamide and serotonin-receptor agonists, also known as triptans, should be used together with caution. Serotonin syndrome has been reported during administration of serotonin-receptor agonists and non-selective monoamine oxidase inhibitors (MAOIs). Since safinamide selectively inhibits MAO-B at recommended doses, no interaction with serotonin-receptor agonists would be expected with normal prescription use. However, monitoring for serotonin-related side effects is advisable since the potential for serotonin syndrome exists. If serotonin syndrome occurs, discontinue all serotonergic agents and institute appropriate treatment.
Zolpidem: (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of safinamide with other sedating medications, such as anxiolytics, sedatives, and hypnotics.